Some 3-10% of Caucasians are deficient in CYP2D6 metabolism (poor metaboliz
ers), due to inheritance of two defective alleles, whereas amplification of
the CYP2D6 gene results in ultrarapid metabolism in 1-2% of Caucasian popu
lations, To examine the possible association between CYP2D6 polymorphism an
d individual smoking behaviour, we analysed the prevalence of CYP2D6 genoty
pes among 292 long-term heavy smokers, 382 individuals with more variable s
moking histories, and 302 never-smokers. The prevalence of ultrarapid metab
olizers in heavy smokers (7.9%) was twofold compared to individuals with va
riable smoking habits (3.7%; odds ratio 2.3, 95% confidence interval 1.2-4.
4), and fourfold compared with never-smokers (2.0%) (odds ratio 4.2, 95% co
nfidence interval 1.8-9.8), The frequency of poor metabolizer genotype was
approximately 2%, in each smoker group. However, when men and women were st
udied separately, the prevalence of poor metabolizer genotype was higher in
male never-smokers (3.6%) than in variable smokers (2.7%) and heavy smoker
s (2.2%), Moreover, a trend test, adjusted by age, gender and cancer status
, revealed a significant trend for the increased tobacco usage with increas
ed metabolic capacity, Our results are in agreement with the assumption tha
t increased CYP2D6 activity may contribute to the probability of being addi
cted to smoking. Pharmacogenetics 10:5-10 (C) 2000 Lippincott Williams & Wi
lliams.